This proposal is to request support for a pair of concurrent 2009 Keystone Symposia meetings entitled Neurodegenerative Diseases: New Molecular Mechanisms (organized by Valina L. Dawson and David M. Holtzman), and Axonal Connections: Molecular Cues for Development and Regeneration (organized by John G. Flanagan, Marie T. Filbin and Liqun Luo), to be held in Keystone, Colorado from February 17 - 22, 2009. Holding these meetings jointly - including a common keynote address and three shared plenary sessions plus considerable shared unstructured time - provides a unique opportunity for bridging an in-depth discussion of neurological disease pathogenesis with a high-level discourse on the molecular and physiological mechanisms governing the normal biology of axon growth and regeneration. The meeting on Neurodegenerative Diseases focuses on significant advances in our understanding of the causes and pathologic progression of neurodegenerative diseases. Identification of disease-causing mutations has provided unprecedented opportunities to develop new and predictive models and move closer to new therapeutic treatments. Technological advances in biochemistry, genomics, proteomics and imaging have facilitated the ability to pose and answer complex questions in complex disease, as well as an appreciation that neurodegenerative diseases have distinct cell death signaling cascades that can share some common molecular events. This meeting will emphasize understanding possible common mechanisms as well as the distinct characteristics of neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), triple repeat diseases, amyotrophic lateral sclerosis (ALS) and others. The meeting on Axonal Connections: Molecular Cues for Development and Regeneration focuses on the normal functioning of the nervous system and, in particular, formation of the complex pattern of connections during development. If such connections are subsequently lost through injury or degeneration, axons in the adult CNS fail to regenerate, creating a major clinical challenge. The last several years have seen tremendous progress in identifying molecular mechanisms for axon development and regeneration, although much remains to be learned about these complex processes. Rapid progress is being made in identifying new classes of extracellular regulators, understanding the mechanisms by which this extracellular information is transduced by the neuron into appropriate responses, and learning the underlying molecular logic for the formation of neural connectivity. These concurrent meetings will bring together researchers in the fields of axon development, degeneration and regeneration;promote exchange of ideas, information and collaboration among these fields;train young scientists in the questions, approaches, and opportunities in these exciting and topical research areas;and promote scientific and translational goals of understanding the basic mechanisms for the formation of neural circuits and developing new strategies for therapeutic repair. PUBLIC HEALTH RELEVANCE: In the USA, neurological disorders affect approximately 50 million Americans and cost an estimated $400 billion annually in medical and related expenses. Unfortunately there are few therapies for individuals who suffer from neurologic disease. Likewise, injury or degeneration in the adult central nervous system (CNS) can cause axons to fail to regenerate, creating a major clinical challenge as the functioning of the nervous system depends on the complex pattern of connections formed during development. These concurrent meetings will bring together researchers in the fields of axon development, degeneration and regeneration;promote exchange of ideas, information and collaboration among these fields;train young scientists in the questions, approaches, and opportunities in these exciting and topical research areas;and promote scientific and translational goals of understanding the basic mechanisms for the formation of neural circuits and developing new strategies for therapeutic repair.